17-47587351-AATATTTTTAAGTGCTCAAAT-A

Position:

• chr17-47587351-AATATTTTTAAGTGCTCAAAT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006310.4(NPEPPS):​c.1095+14_1095+33del variant causes a splice region, intron change. The variant allele was found at a frequency of 0.02 in 151,882 control chromosomes in the GnomAD database, including 84 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (84 hom., cov: 29)
  • Exomes 𝑓: 0.020 (770 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPEPPS NM_006310.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.94

Genes affected

NPEPPS (HGNC:7900): (aminopeptidase puromycin sensitive) This gene encodes the puromycin-sensitive aminopeptidase, a zinc metallopeptidase which hydrolyzes amino acids from the N-terminus of its substrate. The protein has been localized to both the cytoplasm and to cellular membranes. This enzyme degrades enkaphalins in the brain, and studies in mouse suggest that it is involved in proteolytic events regulating the cell cycle. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-47587351-AATATTTTTAAGTGCTCAAAT-A is Benign according to our data. Variant chr17-47587351-AATATTTTTAAGTGCTCAAAT-A is described in ClinVar as [Likely_benign]. Clinvar id is 774350.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPEPPS	NM_006310.4	c.1095+14_1095+33del		splice_region_variant, intron_variant		ENST00000322157.9	NP_006301.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPEPPS	ENST00000322157.9	c.1095+14_1095+33del		splice_region_variant, intron_variant		1	NM_006310.4	ENSP00000320324	P1

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3026 AN: 151764 Hom.: 82 Cov.: 29

Gnomad AFR AF: 0.00504

Gnomad AMI AF: 0.0848

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.0278

GnomAD3 exomes AF: 0.0143 AC: 2533 AN: 177512 Hom.: 9 AF XY: 0.0145 AC XY: 1390 AN XY: 95640

Gnomad AFR exome AF: 0.00200

Gnomad AMR exome AF: 0.00794

Gnomad ASJ exome AF: 0.00932

Gnomad EAS exome AF: 0.0784

Gnomad SAS exome AF: 0.0311

Gnomad FIN exome AF: 0.00975

Gnomad NFE exome AF: 0.00607

Gnomad OTH exome AF: 0.0155

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0204 AC: 28843 AN: 1415674 Hom.: 770 AF XY: 0.0213 AC XY: 14976 AN XY: 702074

Gnomad4 AFR exome AF: 0.00448

Gnomad4 AMR exome AF: 0.0160

Gnomad4 ASJ exome AF: 0.0227

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.0594

Gnomad4 FIN exome AF: 0.0157

Gnomad4 NFE exome AF: 0.0134

Gnomad4 OTH exome AF: 0.0249

GnomAD4 genome AF: 0.0200 AC: 3031 AN: 151882 Hom.: 84 Cov.: 29 AF XY: 0.0219 AC XY: 1627 AN XY: 74238

Gnomad4 AFR AF: 0.00502

Gnomad4 AMR AF: 0.0231

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.0600

Gnomad4 FIN AF: 0.0146

Gnomad4 NFE AF: 0.0147

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0127 Hom.: 2

Bravo AF: 0.0193

Asia WGS AF: 0.0950 AC: 331 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 30, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs202245087; hg19: chr17-45664717;